Shah Pratik, Arya Ved Bhushan, Flanagan Sarah E, Morgan Kate, Ellard Sian, Senniappan Senthil, Hussain Khalid
J Pediatr Endocrinol Metab. 2015 May;28(5-6):695-9. doi: 10.1515/jpem-2014-0371.
Hyperinsulinaemic hypoglycaemia (HH) is the most common cause of severe and persistent hypoglycaemia in neonates. The treatment of severe diazoxide unresponsive HH involves near total pancreatectomy. Mammalian target of rapamycin (mTOR) is a protein kinase that regulates cellular proliferation. mTOR inhibitors are used in cancer patients and recently found to be effective in the treatment of insulinoma and HH patients.
A 36 weeks large for gestational age neonate presented with severe hypoglycaemia on day 1 of life. The hypoglycaemia screen confirmed HH and genetic testing revealed compound heterozygous ABCC8 mutation, confirming diffuse disease. He was unresponsive to the maximal dose of diazoxide (15 mg/kg/day), hence needed treatment with higher concentration of intravenous glucose (25 mg/kg/min), intravenous glucagon and subcutaneous octreotide (30 μg/kg/day) infusions to maintain normoglycaemia. Sirolimus, a mTOR inhibitor, was commenced at 9 weeks of age following which he showed a marked improvement in his glycaemic control. After 4 weeks of sirolimus therapy, he was discharged home on subcutaneous octreotide injection (20 μg/kg/day) and oral sirolimus, thereby avoiding the need for a near total pancreatectomy.
We report the first case of compound heterozygous ABCC8 mutation causing severe diffuse HH that responded to therapy with a mTOR inhibitor.
高胰岛素血症性低血糖症（HH）是新生儿严重持续性低血糖症最常见的病因。对于对二氮嗪无反应的严重HH的治疗包括近乎全胰腺切除术。雷帕霉素哺乳动物靶点（mTOR）是一种调节细胞增殖的蛋白激酶。mTOR抑制剂用于癌症患者，最近发现其对胰岛素瘤和HH患者的治疗有效。
一名孕36周的大于胎龄新生儿在出生第1天出现严重低血糖症。低血糖筛查确诊为HH，基因检测显示复合杂合子ABCC8突变，证实为弥漫性疾病。他对最大剂量的二氮嗪（15毫克/千克/天）无反应，因此需要用更高浓度的静脉葡萄糖（25毫克/千克/分钟）、静脉胰高血糖素和皮下注射奥曲肽（30微克/千克/天）来维持血糖正常。西罗莫司，一种mTOR抑制剂，在9周龄时开始使用，此后他的血糖控制有了显著改善。西罗莫司治疗4周后，他出院回家，接受皮下注射奥曲肽（20微克/千克/天）和口服西罗莫司治疗，从而避免了近乎全胰腺切除术。
我们报告了首例由复合杂合子ABCC8突变导致严重弥漫性HH且对mTOR抑制剂治疗有反应的病例。
